The present invention relates to a method of use in the prevention of or limiting of brain injury due to stroke, preferably as an anesthetic in a subject having an increased risk for stroke, comprising administering to said subject a compound, ketamine, in an effective amount for preventing or reducing the effect of stroke. The compound may be administered in admixture with a pharmaceutically acceptable carrier in a unit dosage form.
Ketamine is well known as a general anesthetic. See, for example, paragraph "5133.Ketamine," The Merck Index, 10th edition, published by Merck and Company, Inc., Rahway, N.J., (1983) page 5138.
This invention is not suggested by the disclosure in, thus is not obvious over the following publications: D. Lodge, et al, "Reduction of Ischemia Induced Brain Damage and of Glutamate Induced Calcium Uptake by Subanesthetic Concentrations of Ketamine," Neuro-Science Letters, Abstracts of the Fourth National Meeting of the Brain Research Association, Birmingham, UK, Apr. 14-16, 1986, supplement 24 (1986), page S35. S. M. Rothman, et al, "Ketamine Blocks Anoxic Neuronal Death in vitro," Stroke, A Journal of Cerebral Circulation, Volumes 17, number 1, January-February (1986), 11th International Joint Conference on Stroke and Cerebral Circulation, p. 124. Particularly, the publications do not disclose or make obvious protective benefits of ketamine as regards stroke because the references do not teach that critical administration of the present invention is before in time the incidence of the stroke and in an amount that is at least sufficient to be said to be behaviorally active in the subject of the stroke.
Thus, the present invention relates to the now discovered novel method of use for the prophylactic treatment of stroke with a compound known as ketamine in an effective amount for preventing or reducing the effect of stroke in unit dosage form.
Additional references regarding related subject matter teach that ketamine acts as a noncompetitive N-methyl-D-aspartate antagonist (NMDA), Martin, D., et al, Neuropharmacology, Vol. 24, No. 10, pp 999-1003 (1985); Thomson, A. M., et al, Nature, Vol. 313, pp 479-481 (7 February 1985); and teach that 2-amino-7-phosphoheptanoic acid (2-APH), also an N-methyl-D-aspartate antagonist, shows prevention of brain damage associated with stroke, SCRIP, number 1067, p 22 (Jan. 13, 1986). However, although a rationale for testing 2-APH in stroke is presented in SCRIP the reference does not suggest the use of ketamine as such for treatment of stroke, and particularly, there is no disclosure to make obvious the critical administration of the present invention.
Further, the present invention is the use of ketamine for treating a subject at risk of stroke as disclosed herein wherein the treatment is administration of ketamine in combination with a benzodiazepine, such as diazepam. Again, although references show the combined use of ketamine and benzodiazepines, Langrehr, D., et al, Acta Anaesthesiologica Belgica, number 2, pp 165-187 (June 1984), the combination is not obvious for use in the present invention administration of ketamine.